Vipoma

KRAS G12D是癌症中最常见的KRAS突变，在胰腺导管腺癌(PDAC)、结直肠癌(CRC)、非小细胞肺癌(NSCLC)中广泛存在，尤其在胰腺癌中较为常见，而且目前尚无针对这些患者的有效靶向疗法。 不过值得欣慰的是，近期美国一款针对KRAS G12D突变的抗癌新药，在治疗胰腺癌的早期临床研究中，获得了高达80%的疾病控制率，具有里程碑式的重大进展！ 一、新型KRAS G12D抑制剂——RMC-9805取得里程碑式进展，胰腺癌控制率高达80% RMC-9805是一款新型口服的 RAS(ON) G12D 选择性共价抑制剂，其在治疗实体瘤领域表现出令人鼓舞的抗肿瘤活性、初始安全性、耐受性。无论作为单一疗法还是联合疗法，RMC-9805在胰腺癌的治疗中，均展现出了惊艳的疗效。 RMC-9805治疗胰腺癌的1/1b 期 RMC-9805-001临床研究（NCT06040541），纳入存在KRAS G12D突变的局部晚期或转移性实体瘤，且既往接受过标准治疗的患者。截至数据截止，单药治疗组共有179例患者接受了递增剂量的 RMC-9805治疗。 结果显示，RMC-9805在 KRAS G12D 突变的胰腺导管腺癌（PDAC）患者中， 客观缓解率（ORR）达到 30% （n = 12）。 疾病控制率（DCR）更是高达80% （n = 32）， 这也意味着80%的胰腺癌患者，在接受RMC-9805治疗后，疾病得到有效控制 （详见下图）！ ▲图源“OneLive”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 二、案例分析 值得一提的是，一位70岁的KRAS G12D突变转移性胰腺癌女性患者，既往曾接受过放化疗、吉西他滨、紫杉醇等治疗，但效果不理想，患者伴肝转移、腹腔动脉及肠系膜上动脉受累，入组接受治疗RMC-9805治疗。 结果显示：ctDNA 基线检测到的KRAS G12D 突变，在治疗第 2 周期， 清除率达到100% ； 肿瘤标志物CA 19-9及CEA 和 急剧下降 ；并最终在 治疗3个周期后，达到部分缓解（PR） （详见下图）。 ▼该患者在RMC-9805治疗前后影像学对比 ▲图源“OneLive”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 三、小编寄语 综上，RMC-9805的初步数据显示，该药对接受过治疗的KRAS G12D 突变型胰腺导管腺癌安全且有效，为胰腺癌患者带来了新的曙光！ 做了基因检测的患者，可立即拿出检测报告查看是否存在KRAS或KRAS G12D突变，看不懂基因检测报告的病友，也可将治疗经历、近期病理及基因检测报告，提交至 全球肿瘤医生网医学部 ，进行初步评估或详细解读报告。 四、参考资料 [1]Jiang L,et al.RMC-9805, a first-in-class, mutant-selective, covalent and oral KRASG12D (ON) inhibitor that induces apoptosis and drives tumor regression in preclinical models of KRASG12D cancers[J]. Cancer research, 2023, 83(7_Supplement): 526-526. https://aacrjournals.org/cancerres/article/83/7_Supplement/526/721097/Abstract-526-RMC-9805-a-first-in-class-mutant [2]https://www.onclive.com/view/rmc-9805-triggers-tumor-regressions-in-kras-g12d-mutant-pancreatic-cancer 本文为全球肿瘤医生网原创，未经授权严禁转载

iStock, hapabapa The regulator cited deficiencies at a third-party manufacturing facility. Camurus is seeking approval for its extended-release subcutaneous formulation of octreotide, which would allow more convenient once-monthly dosing for patients with acromegaly. The FDA has rejected Camurus’ investigational subcutaneous formulation of octreotide, dubbed CAM2029, for the treatment of the rare hormonal disorder acromegaly, the Swedish drugmaker announced on Tuesday. In a Complete Response Letter (CRL), the regulator cited “facility-related deficiencies” discovered last month during an inspection of a third-party manufacturer as the reason for the rejection and did not point to other issues, particularly as regards CAM2029’s clinical efficacy or safety data. The FDA needs to receive “satisfactory” responses from Camurus’ third-party provider before it can resolve the CRL, according to the company. CEO Fredrik Tiberg in a statement called the CRL “disappointing” but noted that the company remains “confident in the data supporting our [New Drug Application] and the potential of CAM2029 to address unmet medical needs of patients with acromegaly.” CRLs from the FDA rejecting drug candidates due to manufacturing issues are on the rise . Out of a total of 238 CRLs issued between 2017 and 2023, 30% involved quality/manufacturing issues —particularly problems with manufacturing processes, facility inspections, or chemical, manufacturing and controls. Camurus will work with its external manufacturer and with the FDA “to bring CAM2029 to patients living with acromegaly as soon as possible,” Tiberg said. To this end, the company said that it has already held labelling discussions with the regulator and that CAM2029’s prescribing information is “well advanced.” Afflicting around sixty patients per one million people, acromegaly is a rare and slowly progressive disease characterized by the abnormal growth of bones and enlarged hands, feet and facial features. Acromegaly also affects internal organs and can typically include symptoms such as headaches, joint pain and fatigue. Acromegaly is often caused by a tumor in the pituitary gland, which leads to the excess production of growth hormone and insulin growth factor-1. When uncontrolled, acromegaly worsens patients’ quality of life or can heighten their risk of death. Octreotide, the active ingredient of CAM2029, is a peptide drug that is well-known as an acromegaly therapy. It works by mimicking the function of somatostatin, a naturally occurring hormone, and activating its corresponding receptor. This mechanism of action helps suppress growth hormone, addressing the underlying cause of acromegaly. Octreotide also lowers the levels and activity of insulin and glucagon. The pharma industry has long taken advantage of octreotide’s therapeutic effects for acromegaly. Sun Pharmaceuticals won FDA approval for Bynfezia Pen (octreotide acetate) in 1988, which is indicated for the three-times-daily subcutaneous treatment of acromegaly. The drug is also approved for carcinoid tumors and vasoactive intestinal peptide tumors. Camurus’ investigational formulation is an extended-release version of octreotide that would allow for once-monthly dosing, giving patients a more convenient treatment option. In the Phase III ACROINNOVA 2 study, CAM2029 led to better biochemical control of acromegaly versus the current standard of care. Camurus’ injection also improved quality of life and symptom burden.

今日（10月21日），加科思发布公告，公司自主研发的KRAS G12C抑制剂戈来雷塞(Glecirasib)被欧洲药品管理局授予胰腺癌孤儿药疗法认定。 胰腺癌是一种恶性程度极高的肿瘤，目前患者缺少有效的标准治疗手段，晚期胰腺癌五年总生存率仅为3.1%。此前，戈来雷塞胰腺癌适应症在美国获得FDA孤儿药疗法认定，并在中国获得国家药监局药审中心突破性疗法认定。戈来雷塞治疗KRAS G12C突变的晚期胰腺癌及其他实体瘤的注册临床试验正在中国的30家中心开展中。 加科思此前在2024年美国临床肿瘤学会胃肠癌研讨会年会(2024 ASCO GI)以口头报告形式公布了二线及以上的KRAS G12C突变胰腺癌患者数据，确认客观缓解率(cORR)为41.9%(13/31)，疾病控制率(DCR)为93.5%(29/31)，中位无进展生存期(mPFS)为5.6个月，中位总生存期(mOS)为10.7个月。 戈来雷塞(JAB-21822)是加科思自主研发的KRAS G12C抑制剂。加科思目前已在中国、美国及欧洲多国启动多项针对携带KRAS G12C突变的晚期实体瘤患者的临床试验，包括与SHP2抑制剂JAB-3312联用治疗非小细胞肺癌(NSCLC)，戈来雷塞与西妥昔单抗在结直肠癌的联合用药，以及单药治疗胰腺癌的注册性临床研究。